Risk of active tuberculosis in patients with inflammatory arthritis receiving TNF inhibitors: a look beyond the baseline tuberculosis screening protocol

Abstract

Tuberculosis (TB) is a major concern in patients receiving TNF inhibitors (TNFi). This study aimed to assess the incidence of active TB and the efficacy of TB prevention measures used over the years, and to determine risk factors for developing TB, in a single-centre cohort of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) receiving TNFi. Data of all patients in whom treatment with TNFi was initiated in our rheumatology clinic until December 1st 2014 have been retrospectively analysed. The cohort was divided into 3 groups per the mandatory LTBI screening method at baseline: tuberculin skin test (TST) with a positive threshold of either 10 mm (group TST1), or 5 mm (group TST2), and QuantiFERON®-TB Gold test (group QFT). The incidence of active TB was analysed for each group and compared to TB incidence data in general population. Five hundred fifty patients were included (305 RA, 42 PsA, 203 AS); 97 patients belonged to the TST1, 229 to the TST2 and 224 to the QFT group. The number of active TB cases/time of exposure to TNFi (person-years, PY) was 8/593.5, 9/1044.0 and 3/555.3, respectively, accounting for an incidence of 1348.0, 862.1 and 540.2 cases per 10 PY. Active TB cases occurring in the first year of TNFi treatment (early TB) per total TB cases were only 3/8, 1/9 and 1/3, respectively, too few to identify statistically significant differences between the 3 LTBI screening protocols. However, less TB cases per total observation time were registered in the QFT group, probably due to the reduced duration of exposure to TNFi. All cases of active TB were registered among patients receiving monoclonal antibodies TNFi agents. We have found no significant risk factors for developing active TB. In our cohort, TB occurring after 1 year of TNFi treatment exceeds 'early TB', suggesting the necessity of further TB prevention measures besides baseline screening for LTBI.

Ankylosing spondylitis and psoriatic arthritis: revisiting screening of latent tuberculosis infection and its follow-up during anti-tumor necrosis factor therapy in an endemic area

“…The analysis of the risk factors for incident TB revealed that known re-exposure is the most critical cause of this complication. It occurred in a median period of 2 years, and we confirmed the previous observation that new TB infections mostly present as a pulmonary disease ( 18 , 33 , 34 ). In contrast, TB reactivation was observed in approximately one-third of the patients with TB, and the majority of cases were extra-pulmonary with a median of 5.3 months of exposure.…”

“…A long-term follow-up was also essential for this evaluation, as TB re-exposure is considered after at least 12 months ( 17 , 18 ), and it has already been shown that the risk remains throughout the treatment ( 19 ). The lack of information regarding the treatment duration ( 3 , 16 , 20 ) precludes an accurate evaluation of the importance of re-exposure in the context of incident TB.…”

Tuberculosis in people with rheumatic disease in Finland 1995–2007: a nationwide retrospective register study

“…Reactivation of latent tuberculosis infection (LTBI) during TNFi treatment was first reported in 2001 and is now well documented [7–9]. This risk can be reduced by routine screening and treatment of LTBI at the start of immunosuppressive treatment [9, 10]. The national Finnish guidelines for screening and treating LTBI in RA patients were published in 2004 [11].…”

An updated systematic review on the applied TST and IGRA Test for diagnosing LTBI in patients treated with TNF-α inhibitor drugs

“…TNF-α antagonists therapy changed a great percentage of indeterminate results of QTF-GT to positive [15]. Ramos [19].…”

“…Active TB has not occurred in patients with positive LTBI. Two subjects with active TB were observed in patients with negative results of TST and QFT-GT The study suggested that LTBI screening and a prophylactic treatment support the safety of biological therapy[18] Soare et al, (2018). assessed the efficacy of TST and QFT-GT for predicting active TB in RA, PsA and AS receiving TNF-α blocker therapy.…”